The skin care industry has long recognized that sunlight exposure increases the risk of wrinkles, age spots, and skin sagging. Such skin damage is photochemical in nature and is associated with high energy, short wavelength light. This light leads to undesirable biochemical changes, such as inflammation and DNA and cell organelle damage. Until the 1970s, the skin care industry considered filtration of UVB radiation sufficient to protect the skin against photo-damage from sunlight exposure. The basis for this conclusion was that a) UVB alone causes redness of the skin (erythema) and b) among the wavelengths of radiation reaching the earth, the region between 280 nm and 320 nm (i.e., UVB) is the most energetic, and thereby the most damaging. A sunscreen active ingredient therefore has been defined as an ingredient that absorbs at least 85 percent of the light in the UV range at wavelengths from 280 to 320 nanometers, but transmits UV light at wavelengths longer than 320 nanometers.
More recently, the skin care industry position regarding photo-damage evolved to include protection against longer-wavelength UVA radiation (320 nm to 400 nm) in addition to protection against UVB. It has been known for some time that UVB, while enabling the skin to produce vitamin D.sub.3, nevertheless also produces erythema (sunburn). If the UVB radiation reaches a threshold dose level termed the minimum erythemal dose (MED), sufficient UVB radiation has been delivered to the skin to cause visible erythema. UVA radiation is orders of magnitude less erythmogenic than UVB radiation, but is nevertheless damaging to the skin. The basis for this position was evidence of DNA damage caused by UVA wavelengths that penetrate deeper into the skin. Therefore, with regard to photodamage to skin from the sun, the prevailing view is that both UVB and UVA radiation should be blocked to prevent damage to the skin.
When considering the effects of UV radiation on the skin, the range of UV wavelengths therefore can be divided into UVA (400-320 nm), also called Long Wave or black light, and UVB (320-280 nm), also called Medium Wave. UVB radiation and UVA radiation both exist in solar light. UVB radiation affects the outer layer of the skin. UVA radiation penetrates deeply into the skin and does not cause sunburn. UVA however can contribute to the aging of skin, DNA damage, and possibly skin cancer. Both UVA and UVB wavelengths can damage collagen fibers. This damage contributes to photo-aging of human skin, which can be reduced by blocking these wavelengths of solar radiation.
The protection of skin from fluorescent lighting also has been suggested (V. Beral, The Lancet, Volume 320, Issue 8293, pages 290-293 (1982).). Although fluorescent light bulbs generally have not been considered to pose a significant UV hazard. Recent studies show significant variation in the spectral output of UV light emissions from 19 different compact fluorescent light bulbs, even within the same class. Although the power output from any given bulb is low, the possible exposure time on a daily basis can be relatively high. The results of the study indicate a potential daily UV dose that ranges from 0.1 to 625 mJ cm.sup.-2, and a daily dose of UVB that ranges from 0.01 to 15 mJ cm.sup.-2. It therefore was concluded that because individuals are exposed to these UV intensities for long periods of time, significant cumulative damage could occur (R. S. Klein et al., Photochemistry and Photobiology, Volume 85, Issue 4, pages 1004-1010, July/August 2009).
UVB sunscreens are evaluated by their ability to prevent erythema, which is how the Sun Protection Factor (SPF) is typically defined. Because UVA radiation does not redden the skin (erythema), its damaging effects cannot be determined by current SPF testing. However, UVA light, because of its longer wavelength, can penetrate deeper into the skin than UVB light and is theorized to be a prime cause of wrinkles. Although, to date, no validated clinical measurement exists to test for the health benefits of blocking UVA radiation, it is important that both UVA and UVB radiation are blocked from the skin.
Present sunscreen formulations typically include a mixture of compounds for absorbing UVA and UVB radiation. Commercially approved formulations include a UVB blocker, such as a p-methoxycinnamate or an aminobenzoate, and a UVA blocker, such as a benzone or an anthranilate. These compounds generally absorb an incoming UV photon and reradiate a lower energy photon. While typically less esthetic, physical blockers, such as zinc oxide, generally provide better screening of light.
Research therefore has focused on UVB and UVA radiation with respect to interaction of sunlight with the skin. However, limiting research efforts to the UVB and UVA wavelength ranges neglects the potential of skin damage from longer wavelength radiation, such as damage caused by visual light (400 nm-700 nm), like premature skin aging and skin cancer. For example, when assessing SPF, wavelengths outside of the UVB-UVA range (290-400 nm) are not tested, thereby missing the deleterious effects of visible and near-infrared wavelengths on the skin.
High energy visible (HEV) light is high frequency light in the violet/blue band from 400 nm to 500 nm in the visible spectrum (400 nm-700 nm). The effect of HEV light on macular degeneration was studied and HEV light has been implicated as a cause in this age related disorder (Glazer-Hockstein et al., Retina 26(1) (2006) pages 1-4). The mechanism by which HEV light damages the lens and the retina is believed to be an accumulation of reactive oxygen species (ROS) due to oxidative damage to cells and their organelles. These changes are irreversible, and therefore should be attenuated and/or prevented. Two recently published studies, conducted to evaluate the effect of HEV light on skin, show that the damaging effects to epidermal and dermal tissue are similar to the damaging effects on the eye (M. Denda et al. J. Invest. Dermatol. 128 (2008) 1335-1336 and L. Zastrow et al. IFSCC Magazine, 11(3) (2008) 297-315).
One recent study (M. Denda et al.) showed that visible radiation (400-700 nm) of different wavelength ranges has different effects on the skin barrier recovery rate of hairless mice after barrier disruption. It was found that blue light (450-500 nm) delayed barrier recovery compared to a control kept in the dark. In particular, the skin barrier repair rate a) decreased with exposure to blue light; b) did not change with green light; and c) increased with red light. The barrier recovery was measured by means of transepidermal water loss (TEWL). In the same study, culture sections of hairless mousse skin were exposed to the same wavelengths. Electron microscopy evaluation revealed that the irradiated skin showed different morphology compared to control skin kept in the dark. It demonstrated a depleted content of intercellular lipids between the stratum corneum (SC) and the stratum granulosum (SG) suggesting the prevention or suppression of processes that support barrier recovery.
The effect of skin exposure to visible light in an ex vivo skin model using human skin obtained from surgery also was studied, and, in particular, the effect of the visible spectra with and without UVA and UVB on the generation of ROS in the skin (L. Zastrow et al.) In this study, high energy (HEV) light in the region of wavelengths between 400 nm and 500 nm that the eye perceives as violet and blue light, contributes significantly to the production of free radicals in the skin. To quantify free radical generation, ESR-X band spectroscopy was utilized. Free radical formation was detected under the influence of all wavelengths from the UVB range to the end of the visible range (280-700 nm). Unexpectedly, the amount of radical formation due to visible light exposure was highly significant. When calculated as part of the spectra of exposure to natural sun light, it showed that UVB generated 4% of ROS, UVA generated 46%, and visible light generated 50% of ROS production. Further identification of the radicals showed that the superoxide anion radical O.sub.2.sup.-. and the hydroxyl radical OH. were produced. Generation of these two highly reactive species can lead to a chain reaction and generation of other biological radicals, including secondary lipid radicals .CH—R in different skin layers. ROS production is well known to be involved in premature skin aging, often accompanied by inflammatory cascades, generation of age spots and wrinkles, and in the promotion of cancerous skin lesions.
The above studies were conducted independently of one another and led to two conclusions: (a) HEV-light accelerates skin aging by an overexpression of damaging free radicals (at the deep live epidermis and dermis layers) and (b) HEV light leads to a compromised skin barrier (at the stratum corneum and upper live epidermal layers). These two processes are known to be involved in skin aging. Overall, it has been suggested that HEV light causes as much skin damage as UVA and UVB radiation combined.
While the cosmetic and personal care industry has been focusing on the improvement of sun protecting formulations to efficiently block exposure to UVB and UVA light, it has neglected the effects of visible light on the skin and the formulation of compositions that shield the skin from HEV wavelengths. Furthermore, in order to protect the skin from visible light, persons in the art expect that a compound or composition would be dark in color. Providing a darkly colored composition for application to the skin, presents a constraint on consumer acceptance, whereas UV filtration imparts no color to a skin care product. For example, melanin has been disclosed for use in skin care products based upon a) the UV-absorbing character of melanin and b) the fact that melanin is a natural product for protection against sunlight damage. However, the color of such products was not consumer acceptable.
A need therefore exists in the art to provide compounds and compositions that protect skin from HEV light in sunlight and in artificial lighting that contains larger amounts of HEV light. Accordingly, provided herein are novel melanin derivatives having an esthetically acceptable light yellow color in formulated compositions, like skin care products, and that effectively absorb light in the HEV range.